Rats as models for human disease have made valuable contributions to almost every field of human medicine. Recently, major advances have been made in developing reagents, genomic information, and critical germline modification techniques for the rat, including making transgenic animals. With these tools in place, rat models can make unprecedented contributions toward understanding the molecular basis of human disease and targeting development of new therapeutic strategies. Unfortunately, there are several major impediments to realization of the full potential of rats as models of human disease: 1) Many inbred and genetically engineered rat strains are not available to researchers. While commercial producers maintain inventories of commonly used rat strains, less commonly used strains are frequently unavailable to researchers. 2) While individual investigators develop and characterize many mutant rat models, they lack the physical and financial resources to maintain potentially important strains. 3) Gene knockouts are not currently possible in the rat. 4) Quality control with respect to infectious diseases is often lacking. Taken together, these impediments document the clear need for a resource center that can provide high quality rat strains to the biomedical community and develop techniques needed for advancement of rats as models. The overall goal of this application is to establish a Rat Resource & Research Center (RRRC). This center will meet the needs of the biomedical research community by developing the infrastructure for distributing high quality, well-characterized inbred, hybrid and genetically engineered rat (GER) to investigators, either as live rats or as cryopreserved germplasm, and by performing innovative research that generates new information which will benefit the RRRC and the scientific community. To accomplish this goal, an established multidisciplinary consortium: the Cryobiology Research Institute at Indiana University (CRI), Harlan Sprague Dawley Inc. (HSD), Memorial Institute for Education and Research (CMIER) at Northwestern University Medical School, will develop a RRRC. This unique consortium has extensive expertise in each of the disciplines needed, including importation, rederivation, breeding, embryo and gamete cryopreservation, genotyping, phenotyping, infectious disease monitoring, and distribution of laboratory rats. The RRRC will provide an uninterrupted supply of rats to biomedical investigators. Research projects aimed at improving rat nuclear transfer and developing rat knockout models, cryobiology, and health monitoring of rats will be performed. Results will benefit investigators worldwide.